Comparison of efficacy and safety among four therapeutic regimens in primary membranous nephropathy with high anti-PLA2R antibody titers: a single-center retrospective cohort study.

BACKGROUND: Patients with primary membranous nephropathy (PMN) and high anti-PLA2R antibody titers (> 150 RU/mL) often respond poorly to conventional treatments, and the optimal immunosuppressive regimen remains unclear. We conducted a retrospective study to compare the efficacy and safety of four regimens in this high-risk population: rituximab monotherapy (RTX regimen), tacrolimus plus glucocorticoids (TAC regimen), rituximab plus cyclosporine (RTX plus CsA regimen), and cyclophosphamide plus glucocorticoids (CTX regimen). METHODS: We retrospectively enrolled 185 patients with biopsy-proven PMN and anti-PLA2R titers > 150 RU/mL. All patients completed the full treatment course and the 24-month follow-up period. The primary outcome was total remission (TR) at 24 months, and the secondary outcomes included complete remission (CR), partial remission (PR), immunological remission (IR), relapse rate, time to remission, and adverse events. RESULTS: At 24 months, the TR rates were 54.5% (24/44) for the RTX regimen, 52.2% (24/46) for the TAC regimen, 76% (38/50) for the RTX plus CsA regimen, and 73.3% (33/45) for the CTX regimen. Kaplan-Meier analysis revealed significant differences in cumulative IR rate (log-rank P = 0.0009), cumulative CR rate (log-rank P = 0.0072), and cumulative TR rate (log-rank P = 0.0005) among the four regimens. The TAC regimen had a significantly higher relapse rate (36.8%, 14/38) than the RTX plus CsA regimen (13.6%, 6/44) (log-rank P = 0.013). CONCLUSION: In this retrospective cohort, the RTX plus CsA regimen demonstrated durable efficacy, with a more favorable safety profile and a lower relapse rate. These preliminary findings support formal comparison of this regimen with current therapies in randomized controlled trials (RCTs).